Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.

Détails

Ressource 1Télécharger: e201800164.full.pdf (2046.61 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_8398D98F5515
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.
Périodique
Life Science Alliance
Auteur(s)
Dubrot J., Duraes F.V., Harlé G., Schlaeppi A., Brighouse D., Madelon N., Göpfert C., Stokar-Regenscheit N., Acha-Orbea H., Reith W., Gannagé M., Hugues S.
ISSN
2575-1077 (Electronic)
ISSN-L
2575-1077
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
1
Numéro
6
Pages
e201800164
Langue
anglais
Résumé
How lymph node stromal cells (LNSCs) shape peripheral T-cell responses remains unclear. We have previously demonstrated that murine LNSCs, lymphatic endothelial cells (LECs), blood endothelial cells (BECs), and fibroblastic reticular cells (FRCs) use the IFN-γ-inducible promoter IV (pIV) of the MHC class II (MHCII) transactivator CIITA to express MHCII. Here, we show that aging mice (>1 yr old) in which MHCII is abrogated in LNSCs by the selective deletion of pIV exhibit a significant T-cell dysregulation in LNs, including defective Treg and increased effector CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell frequencies, resulting in enhanced peripheral organ T-cell infiltration and autoantibody production. The proliferation of LN-Tregs interacting with LECs increases following MHCII up-regulation by LECs upon aging or after exposure to IFN-γ, this effect being abolished in mice in which LECs lack MHCII. Overall, our work underpins the importance of LNSCs, particularly LECs, in supporting Tregs and T-cell tolerance.
Pubmed
Open Access
Oui
Création de la notice
20/01/2019 16:59
Dernière modification de la notice
20/08/2019 15:43
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